Apparatus and method for ventricular rate regularization

ABSTRACT

A cardiac rhythm management device which employs pacing therapy to regularize the ventricular rhythm. Such ventricular rate regularization may be employed within bradycardia pacemakers, ventricular resynchronization devices, or implantable cardioverter/defibrillators.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is a continuation of U.S. patent application Ser. No.10/394,497, filed on Mar. 20, 2003, which is a continuation-in-part ofthe following co-pending, commonly assigned patent applications: U.S.patent application Ser. No. 09/316,515, filed on May 21, 1999, entitled“Method and Apparatus for Treating Irregular Ventricular ContractionsSuch as During Atrial Arrhythmia,” now issued as U.S. Pat. No.7,062,325, and U.S. patent application Ser. No. 09/792,651, nowabandoned, filed on Feb. 23, 2001, entitled “Apparatus and Method forVentricular Rate Regularization,” which disclosures are hereinincorporated by reference in their entirety.

By virtue of the preceding statement, the following issued patents areincorporated by reference into the present disclosure: U.S. Pat. Nos.6,351,669 and 6,285,907.

FIELD OF THE INVENTION

This invention pertains to cardiac rhythm management devices and methodsfor operating such devices. In particular, the invention relates tomethods for employing pacing therapy to maintain hemodynamic stability.

BACKGROUND

The human heart normally maintains its own well-ordered intrinsic rhythmthrough generation of stimuli by pacemaker tissue that results in a waveof depolarization that spreads through specialized conducting tissue andthen into and through the myocardium. The well-ordered propagation ofelectrical depolarizations through the heart causes coordinatedcontractions of the myocardium that results in the efficient pumping ofblood. In a normally functioning heart, stimuli are generated under theinfluence of various physiological regulatory mechanisms to cause theheart to beat at a rate that maintains cardiac output at a levelsufficient to meet the metabolic needs of the body. Abnormalities ofexcitable cardiac tissue, however, can lead to abnormalities of heartrhythm that are called arrhythmias. All arrhythmias stem from one of twocauses: abnormalities of impulse generation or abnormalities of impulsepropagation. Arrhythmias can cause the heart to beat too slowly(bradycardia, or a bradyarrhythmia) or too quickly (tachycardia, or atachyarrhythmia), either of which may cause hemodynamic compromise ordeath.

Drug therapy is often effective in preventing the development ofarrhythmias and in restoring normal heart rhythms once an arrhythmia hasoccurred. However, drug therapy is not always effective for treatingparticular arrhythmias, and drug therapy usually causes side-effectsthat may be intolerable in certain patients. For such patients, analternative mode of treatment is needed. One such alternative mode oftreatment includes the use of an implantable cardiac rhythm managementdevice that delivers therapy to the heart in the form of electricalstimuli. Such devices include cardiac pacemakers that deliver timedsequences of low energy electrical stimuli, called pacing pulses, to theheart via an intravascular lead having one or more electrodes that aredisposed in the myocardium of the paced chamber. Heart contractions areinitiated in response to such pacing pulses, and by properly timing thedelivery of the pacing pulses, the heart can be made to contract inproper rhythm, greatly improving its efficiency as a pump. Suchpacemakers are often used to treat patients with bradycardia due eitherto conduction abnormalities (e.g., AV block) or to sinus nodedysfunction.

Cardiac rhythm management devices may also be used in the treatment oftachyarrhythmias such as tachycardia (i.e., a heart rate that is toorapid). Pacemakers, for example, can be configured to deliver paces tothe heart in such a manner that the heart rate is slowed, a pacing modereferred to as anti-tachycardia pacing. Another class of cardiac rhythmmanagement devices, implantable cardioverter/defibrillators (ICD's),deliver high energy electrical stimuli to the heart in order toterminate fibrillation, which is the most extreme form oftachyarrhythmia. Fibrillation, which may occur in either the atria orthe ventricles, refers to the situation where electrical activityspreads through the myocardium in a disorganized fashion so thateffective contraction does not occur. An ICD delivers a high energyelectrical stimulus or shock to either the atria or ventricles in orderto terminate the fibrillation, allowing the heart to reestablish anormal rhythm for the efficient pumping of blood. In addition to ICD'sand pacemakers, cardiac rhythm management systems also includepacemaker/ICD's that combine the functions of pacemakers and ICD's, drugdelivery devices, and any other implantable or external systems ordevices for diagnosing, monitoring, or treating cardiac arrhythmias.

Irregular ventricular tachycardia, in which the ventricles beat morerapidly and irregularly than normal, can be due to a variety ofetiologies. Certain patients, for example, are prone to prematureventricular contractions due to ectopic excitatory foci in theventricular myocardium. Another cause of ventricular tachycardia isatrial fibrillation. The intrinsic ventricular rhythm that occurs duringan episode of atrial fibrillation is a result of the chaoticallyoccurring depolarizations occurring in the atria being passed throughthe AV node to the ventricles. The intrinsic ventricular rate is thengoverned by the cycle length of the atrial fibrillation and therefractory period of the AV node. Although the intrinsic ventricularrate is less than the atrial rate, due to the refractory period of theAV node, it is still rapid and irregular. When the ventricles contractat irregular intervals, the contraction can occur prematurely beforediastolic filling is complete which decreases the stroke volume for thatcontraction. This can be especially significant in, for example,congestive heart failure patients who are already hemodynamicallycompromised. Concomitant atrial fibrillation where the atria no longeract as effective priming pumps can also contribute to the problem. Anirregular ventricular rate can thus depress cardiac output and causesuch symptoms as dyspnea, fatigue, vertigo, and angina.

An objective of the present invention is to use pacing therapy tomaintain hemodynamic stability in the presence of an irregular intrinsicventricular rhythm. Such pacing therapy may be used in conjunction withany type of cardiac rhythm management device that is capable ofdelivering ventricular paces.

SUMMARY OF THE INVENTION

The present invention is a system and method for regularizing theventricular rate by adjusting the lower rate limit of a pacemakerconfigured to deliver ventricular paces in accordance with changes inthe measured intrinsic ventricular rate. By making the ventricularescape interval track a mean interval between intrinsic beats, lessvariability in the overall ventricular rhythm is allowed by thepacemaker. Ventricular rate regularization may be used to improvecardiac output when used with conventional bradycardia pacing and mayalso be used to improve the efficacy of ventricular resynchronizationtherapy. Cardiac rhythm management devices configured to specificallytreat atrial or ventricular tachyarrhythmias with defibrillation shocksmay also advantageously employ ventricular rate regularization.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an exemplary filter implementation of a ventricular rateregularization system.

FIG. 2 is a system diagram of a microprocessor-based cardiac rhythmmanagement device.

FIGS. 3A through 3D are block diagrams illustrating exemplary componentsof different cardiac rhythm management devices employing ventricularrate regularization therapy.

DETAILED DESCRIPTION

As will be described below, ventricular rate regularization may beadvantageously applied together with a number of different cardiacrhythm management therapies. Ventricular rate regularization therapymay, for example, be implemented in a device configured to deliverconventional bradycardia pacing therapy to the atria and/or ventricles.Ventricular rate regularization may also be implemented in a deviceconfigured to deliver atrial or ventricular resynchronization therapy,where it has special advantages. Devices configured to deliveranti-tachyarrhythmia therapy in the form of ventricular defibrillationshocks may also use ventricular rate regularization when an irregularventricular rate is detected that does not warrant a defibrillationshock. Finally, ventricular rate regularization is useful whenimplemented by an implantable atrial cardioverter/defibrillator both inmaintaining hemodynamic stability when an episode of atrial fibrillationoccurs and in facilitating the delivery of an atrial defibrillationshock synchronized with an R-wave.

1. Bradycardia Pacing Modes

Bradycardia pacing modes refer to pacing algorithms used to pace theatria and/or ventricles when the intrinsic ventricular rate isinadequate either due to AV conduction blocks or sinus node dysfunction.Such modes may either be single-chamber pacing, where either an atriumor a ventricle is paced, or dual-chamber pacing in which both an atriumand a ventricle are paced. The modes are generally designated by aletter code of three positions where each letter in the code refers to aspecific function of the pacemaker. The first letter refers to whichheart chambers are paced and which may be an A (for atrium), a V (forventricle), D (for both chambers), or O (for none). The second letterrefers to which chambers are sensed by the pacemaker's sensing channelsand uses the same letter designations as used for pacing. The thirdletter refers to the pacemaker's response to a sensed P wave from theatrium or an R wave from the ventricle and may be an I (for inhibited),T (for triggered), D (for dual in which both triggering and inhibitionare used), and O (for no response). Modem pacemakers are typicallyprogrammable so that they can operate in any mode which the physicalconfiguration of the device will allow. Additional sensing ofphysiological data allows some pacemakers to change the rate at whichthey pace the heart in accordance with some parameter correlated tometabolic demand. Such pacemakers are called rate-adaptive pacemakersand are designated by a fourth letter added to the three-letter code, R.

Pacemakers can enforce a minimum heart rate either asynchronously orsynchronously. In asynchronous pacing, the heart is paced at a fixedrate irrespective of intrinsic cardiac activity. There is thus a riskwith asynchronous pacing that a pacing pulse will be deliveredcoincident with an intrinsic beat and during the heart's vulnerableperiod which may cause fibrillation. Most pacemakers for treatingbradycardia today are therefore programmed to operate synchronously in aso-called demand mode where sensed cardiac events occurring within adefined interval either trigger or inhibit a pacing pulse. Inhibiteddemand pacing modes utilize escape intervals to control pacing inaccordance with sensed intrinsic activity. In an inhibited demand mode,a pacing pulse is delivered to a heart chamber during a cardiac cycleonly after expiration of a defined escape interval during which nointrinsic beat by the chamber is detected. If an intrinsic beat occursduring this interval, the heart is thus allowed to “escape” from pacingby the pacemaker. Such an escape interval can be defined for each pacedchamber. For example, a ventricular escape interval can be definedbetween ventricular events so as to be restarted with each ventricularsense or pace. The inverse of this escape interval is the minimum rateat which the pacemaker will allow the ventricles to beat, sometimesreferred to as the lower rate limit (LRL).

In atrial tracking pacemakers (i.e., VDD or DDD mode), anotherventricular escape interval is defined between atrial and ventricularevents, referred to as the atrio-ventricular interval (AVI). Theatrio-ventricular interval is triggered by an atrial sense or pace andstopped by a ventricular sense or pace. A ventricular pace is deliveredupon expiration of the atrio-ventricular interval if no ventricularsense occurs before. Atrial-tracking ventricular pacing attempts tomaintain the atrio-ventricular synchrony occurring with physiologicalbeats whereby atrial contractions augment diastolic filling of theventricles. If a patient has a physiologically normal atrial rhythm,atrial-tracking pacing also allows the ventricular pacing rate to beresponsive to the metabolic needs of the body.

A pacemaker can also be configured to pace the atria on an inhibiteddemand basis. An atrial escape interval is then defined as the maximumtime interval in which an atrial sense must be detected after aventricular sense or pace before an atrial pace will be delivered. Whenatrial inhibited demand pacing is combined with atrial-triggeredventricular demand pacing (i.e., DDD mode), the lower rate interval isthen the sum of the atrial escape interval and the atrio-ventricularinterval.

Finally, rate-adaptive algorithms may be used in conjunction withbradycardia pacing modes. Rate-adaptive pacemakers modulate theventricular and/or atrial escape intervals based upon measurementscorresponding to physical activity. Such pacemakers are applicable tosituations in which atrial tracking modes cannot be use. In arate-adaptive pacemaker operating in a ventricular pacing mode, the LRLis adjusted in accordance with exertion level measurements such as froman accelerometer or minute ventilation sensor in order for the heartrate to more nearly match metabolic demand. The adjusted LRL is thentermed the sensor-indicated rate.

2. Ventricular Rate Regularization

Ventricular rate regularization (VRR) is a ventricular pacing mode inwhich the LRL of the pacemaker is dynamically adjusted in accordancewith a detected intrinsic ventricular rate. When a pacemaker isoperating in a ventricular demand pacing mode (e.g., VVI), intrinsicventricular beats occur when the instantaneous intrinsic rate risesabove the LRL of the pacemaker. Thus, paces can be interspersed withintrinsic beats, and the overall ventricular rhythm as a result of bothpaces and intrinsic beats is determined by the LRL and the mean valueand variability of the intrinsic ventricular rate. VRR regularizes theoverall ventricular rhythm by adjusting the LRL of the pacemaker inaccordance with changes in the measured intrinsic rate.

The intrinsic ventricular rate is the rate at which intrinsicventricular beats occur and can be defined both instantaneously and asbeing at some mean value with a certain variability about that mean. Theinstantaneous intrinsic rate can be determined by measuring an R-Rinterval, where an R-R interval is the time between a presentventricular sense (i.e., an R-wave or intrinsic ventriculardepolarization) and the preceding ventricular sense or ventricular pace,with the instantaneous rate being the reciprocal of the measuredinterval. The mean intrinsic rate can be determined by averaging theinstantaneous R-R intervals over a period of time. The LRL of apacemaker is initially set to a programmed base value and defines theventricular escape interval, which is the maximum time betweenventricular beats allowed by the pacemaker and is the reciprocal of theLRL. At any particular mean intrinsic rate above the LRL, a ventricularpace is delivered only when, due to the variability in the intrinsicrate, an R-R interval would be longer than the ventricular escapeinterval were it allowed to occur. As the mean intrinsic ventricularrate increases above the LRL, fewer paces are delivered and morevariability in the overall ventricular rhythm is allowed. The VRR pacingmode counteracts this by increasing the LRL as the mean intrinsicventricular rate increases to thereby increase the frequency of pacedbeats which decreases the incidence of long intrinsic R-R intervals andthus lessens the variability in the overall ventricular rate. The VRRmode then decreases the LRL toward its base value as the number of pacesdelivered increases due to a decrease in either the mean intrinsicventricular rate or its variability. The LRL adjusted in this manner isalso referred to herein as the VRR-indicated rate.

In one embodiment of VRR, the LRL is adjusted to increase toward aprogrammed maximum value by measuring an R-R interval when a ventricularsense occurs and then computing an updated ventricular escape intervalbased upon the measured R-R interval. When a ventricular pace isdelivered, on the other hand, the Is LRL is made to decay toward theprogrammed base value. FIG. 1 shows an exemplary implementation of a VRRsystem made up of a pair of filters 515 and 516 which may be implementedas software executed by the controller 10 (a.k.a. firmware) and/or withdiscrete components. Filter 515 is employed to compute the updatedventricular escape interval when a ventricular sense occurs, and filter516 is used when a ventricular pace is delivered.

When a ventricular sense occurs, the measured R-R interval is input to arecursive digital filter 515 whose output is the updated ventricularescape interval. The filter 515 multiplies the measured R-R interval bya filter coefficient A and then adds the result to the previous value ofthe output (i.e., the present ventricular escape interval) multiplied bya filter coefficient B. The operation of the filter is thus described byVEI_(n)=A(RR_(n))+B(VEI_(n-1)), where A and B are selected coefficients,RR_(n) is the most recent R-R interval duration, and VEI_(n-1) is theprevious value of the ventricular escape interval. A useful way toconceptualize the filter 515 is to decompose the coefficients A and Binto a scaling factor a and a weighting coefficient w such that A=a·wand B=(1−w), where w is between 0 and 1. Viewed this way, the filter isseen as computing a weighted average of the present R-R intervalmultiplied by the scaling factor a and the present ventricular escapeinterval. The filter thus causes the value of the ventricular escapeinterval to move toward the present R-R interval multiplied by thescaling factor at a rate determined by the weighting coefficient. Thiscorresponds to the filter moving the pacemaker's LRL toward a fraction1/a of the instantaneous intrinsic ventricular rate, up to a maximumpacing rate MPR, as determined by the measured R-R interval. If aventricular sense has occurred, the current LRL is necessarily less thanthe measured instantaneous intrinsic ventricular rate. If it is alsoless than 1/a of the intrinsic rate, the LRL is increased by the filterup to a value that is 1/a of the intrinsic rate (as limited by the MPR)to result in more pacing and less variability in the overall ventricularrhythm.

When a ventricular pace is delivered due to expiration of theventricular escape interval without a ventricular sense, filter 516multiplies the present ventricular escape interval by a filtercoefficient C so that VEI_(n)=C(VEI_(n-1)). To provide stable operation,the coefficient C must be set to a value greater than 1. Filter 516 thencauses the ventricular escape interval to increase in an exponentialmanner with each pace as successive values of the escape interval areinput to the filter up to a value corresponding to the base LRL.

The updating of the ventricular escape interval may be performed invarious ways including on a beat-to-beat basis, at periodic intervals,or with averages of successive R-R intervals. In a presently preferredembodiment, however, the updating is performed on a beat-to-beat basiswith each ventricular sense or pace causing adjustment of the LRL byfilter 515 or 516, respectively. The two filters operating together thuscause the LRL to move closer to 1/a of the measured intrinsic rate (upto the MPR) after a ventricular sense and to decay toward the base LRLvalue after a ventricular pace.

The coefficients a and w (or A and B) and C are selected by the user andmay be made programmable so that the behavior of the system can beadjusted to produce the clinically best result in an individual patient.For example, as the scaling factor a is made greater than 1, the filter515 causes the LRL to move toward a smaller fraction 1/a of the detectedintrinsic rate which allows more intrinsic beats to occur and greatervariability in the overall rhythm. As a is decreased back toward 1, thefilter 515 tends to move the LRL of the pacemaker toward a largerfraction of the detected instantaneous intrinsic rate, thus increasingthe amount of pacing and decreasing the amount of variability allowed inthe overall ventricular rhythm. If a is made smaller than 1, the LRL ismoved toward a rate higher than the intrinsic rate, further increasingthe amount of pacing to a point where most of the ventricular rhythm ismade up of paced beats. The larger the weighting factor w, the fasterthe LRL is moved to the specified fraction of the intrinsic rate, makingthe system more responsive to increases in the variability of theintrinsic rhythm. The larger the decay coefficient C, the more rapidlywill filter 516 cause the LRL to decrease toward its programmed basevalue when ventricular paces are delivered due to no ventricular sensesbeing detected within the ventricular escape interval. The controllerlimits the updated ventricular escape interval as a result of theoperations of filters 515 and 516 to minimum and maximum values inaccordance with the programmed maximum pacing rate MPR and base lowerrate limit LRL, respectively.

As noted, the coefficients of filters 515 and 516 can be madeprogrammable by the user, such as by using a remote programmer. Inanother embodiment, the user selects a desired performance parameter(e.g., desired degree of rate regularization, desired amount of pacing,desired decay rate, etc.) from a corresponding range of possible values.The appropriate combinations of coefficients for filters 515 and 516 arethen automatically selected to provide filter settings that correspondto the selected user-programmed performance parameter. The filtercoefficients can also be made functions of other parameters, such as themeasured R-R interval and current LRL setting, and dynamically adjusted.

The VRR system in this embodiment uses the programmed base LRL of thepacemaker as the lower limit to which the LRL is permitted to decay whenno ventricular senses are detected. The base LRL can be changedperiodically by the user with an external programmer, and certainpacemakers also have the capability of dynamically adjusting the LRL inorder to adapt to exercise. In such rate-adaptive pacemakers, the LRL isadjusted in accordance with exertion level measurements such as from anaccelerometer or minute ventilation sensor in order for the heart rateto more nearly match metabolic demand. The adjusted LRL is then termedthe sensor-indicated rate. If a rate-adaptive pacemaker is operated in aVRR mode, the sensor-indicated rate can simply be regarded by thepacemaker as the base LRL. The lower limit for the VRR-indicated rate isthen the sensor-indicated rate rather than the programmed base LRL.

3. System Description

FIG. 2 shows a system diagram of a microprocessor-based cardiac rhythmmanagement device suitable for delivering ventricular rateregularization therapy as well as various cardiac rhythm managementtherapies with which ventricular rate regularization can beadvantageously combined. In the particular embodiments to be describedbelow, a device incorporating the present invention may possess all ofthe components shown in FIG. 2 or only those necessary to perform thefunctions described.

The controller 10 of the device is a microprocessor which communicateswith a memory 12 via a bidirectional data bus. The memory 12 typicallycomprises a ROM (read-only memory) for program storage and a RAM(random-access memory) for data storage. The operation of the controllerconstitutes circuits for sensing and pacing both atria and bothventricles. The pacemaker has atrial sensing and pacing channelscomprising electrode 34 a-b, leads 33 a-b, sensing amplifiers 31 a-b,pulse generators 32 a-b, and atrial channel interfaces 30 a-b whichcommunicate bidirectionally with microprocessor 10. The device also hasventricular sensing and pacing channels for both ventricles comprisingelectrodes 24 a-b, leads 23 a-b, sensing amplifiers 21 a-b, pulsegenerators 22 a-b, and ventricular channel interfaces 20 a-b. In thefigure, “a” designates one ventricular or atrial channel and “b”designates the channel for the contralateral chamber. In thisembodiment, a single electrode is used for sensing and pacing in eachchannel, known as a unipolar lead. Other embodiments may employ bipolarleads which include two electrodes for outputting a pacing pulse and/orsensing intrinsic activity. The channel interfaces 20 a-b and 30 a-binclude analog-to-digital converters for digitizing sensing signalinputs from the sensing amplifiers and registers which can be written toby the microprocessor in order to output pacing pulses, change thepacing pulse amplitude, and adjust the gain and threshold values for thesensing amplifiers. An exertion level sensor 330 (e.g., an accelerometeror a minute ventilation sensor) enables the controller to adapt thepacing rate in accordance with changes in the patient's physicalactivity. A telemetry interface 40 is also provided for communicatingwith an external programmer 500 which has an associated display 510. Aswill be discussed more fully below, the device of FIG. 2 is alsoconfigured to deliver anti-tachyarrhythmia therapy by anti-tachycardiapacing and/or cardioversion/defibrillation.

4. Bradycardia Pacing With VRR

VRR can be employed to modify conventional bradycardia pacing in orderto improve the deleterious hemodynamic effects brought about by anirregular intrinsic ventricular rhythm. FIG. 3A is a conceptual blockdiagram illustrating some exemplary components of a pacemaker foroperating in an inhibited demand ventricular pacing mode. Thesecomponents may be implemented in firmware executed by the controller 10of FIG. 2 or by a combination of firmware and discrete logic components.A supervisory controller program executed by the controller 10 of FIG. 2controls the overall operation of the system in order to implementvarious pacing modes. (Not represented in the figure are othercomponents that may be necessary for other pacing modes, e.g., atrialsensing and pacing channels.) Pacing is controlled by the VEI timer A1that expires after the programmed ventricular escape interval haselapsed and sends a signal to the ventricular pace output module A2. Ifventricular pacing is enabled, the pace output module A2 causes theventricular pacing channel A4 to deliver a ventricular pace. The VEItimer A1 is resets automatically after expiration and upon receiving asignal from R-wave detector A3. The R-wave detector A3 determines ifsensing signals from the ventricular sensing channel A5 exceed aspecified threshold and should therefore be interpreted as an R-wave.With these components, a ventricular pacing mode such as VVI may beimplemented.

In order to also implement VRR, filters 515 and 516 are enabled by thesupervisory controller program. Filters 515 and 515, as described abovewith respect to FIG. 1, update the ventricular escape interval of VEItimer A1 in accordance with whether a pace is delivered upon expirationof the ventricular escape interval or an intrinsic ventricular beatoccurs. If VRR has been enabled, expiration of the VEI timer causesupdating of the ventricular escape interval by filter 516 (which tendsto increase the escape interval), while receipt of an R-wave due to anintrinsic beat causes filter 515 to update the escape interval basedupon the R-R interval determined by the R-R interval detector A6.

5. Cardiac Resynchronization Therapy with VRR

Heart failure is clinical syndrome in which an abnormality of cardiacfunction causes cardiac output to fall below a level adequate to meetthe metabolic demand of peripheral tissues and is usually referred to ascongestive heart failure (CHF) due to the accompanying venous andpulmonary congestion. CHF can be due to a variety of etiologies withischemic heart disease being the most common. Some CHF patients sufferfrom some degree of AV block or are chronotropically deficient such thattheir cardiac output can be improved with conventional bradycardiapacing. Such pacing, however, may result in some degree ofuncoordination in atrial and/or ventricular contractions due to the wayin which pacing excitation is typically spread throughout the myocardiumwithout the benefit of the heart's specialized conduction system. Theresulting diminishment in cardiac output may be significant in a CHFpatient whose cardiac output is already compromised. Intraventricularand/or interventricular conduction defects (e.g., bundle branch blocks)are also commonly found in CHF patients. In order to treat theseproblems, cardiac rhythm management devices have been developed whichprovide pacing stimulation to one or more heart chambers in an attemptto improve the coordination of atrial and/or ventricular contractions,termed cardiac resynchronization therapy.

Cardiac resynchronization therapy is pacing stimulation applied to oneor more heart chambers in a manner that restores or maintainssynchronized bilateral contractions of the atria and/or ventricles andthereby improves pumping efficiency. Certain patients with conductionabnormalities may experience improved cardiac synchronization withconventional single-chamber or dual-chamber pacing as described above.For example, a patient with left bundle branch block may have a morecoordinated contraction of the ventricles with a pace than as a resultof an intrinsic contraction. In that sense, conventional bradycardiapacing of an atrium and/or a ventricle may be considered asresynchronization therapy. Resynchronization pacing, however, may alsoinvolve pacing both ventricles and/or both atria in accordance with asynchronized pacing mode as described below. A single chamber may alsobe resynchronized to compensate for intra-atrial or intra-ventricularconduction delays by delivering paces to multiple sites of the chamber.

It is advantageous to deliver resynchronization therapy in conjunctionwith one or more synchronous bradycardia pacing modes, such as aredescribed above. One atrial and/or one ventricular pacing sites aredesignated as rate sites, and paces are delivered to the rate sitesbased upon pacing and sensed intrinsic activity at the site inaccordance with the bradycardia pacing mode. In a single-chamberbradycardia pacing mode, for example, one of the paired atria or one ofthe ventricles is designated as the rate chamber. In a dual-chamberbradycardia pacing mode, either the right or left atrium is selected asthe atrial rate chamber and either the right or left ventricle isselected as the ventricular rate chamber. The heart rate and the escapeintervals for the pacing mode are defined by intervals between sensedand paced events in the rate chambers only. Resynchronization therapymay then be implemented by adding synchronized pacing to the bradycardiapacing mode where paces are delivered to one or more synchronized pacingsites in a defined time relation to one or more selected sensing and/orpacing events that either reset escape intervals or trigger paces in thebradycardia pacing mode. Multiple synchronized sites may be pacedthrough multiple synchronized sensing/pacing channels, and the multiplesynchronized sites may be in the same or different chambers as the ratesite.

In bilateral synchronized pacing, which may be either biatrial orbiventricular synchronized pacing, the heart chamber contralateral tothe rate chamber is designated as a synchronized chamber. For example,the right ventricle may be designated as the rate ventricle and the leftventricle designated as the synchronized ventricle, and the paired atriamay be similarly designated. Each synchronized chamber is then paced ina timed relation to a pace or sense occurring in the contralateral ratechamber.

One synchronized pacing mode may be termed offset synchronized pacing.In this mode, the synchronized chamber is paced with a positive,negative, or zero timing offset as measured from a pace delivered to itspaired rate chamber, referred to as the synchronized chamber offsetinterval. The offset interval may be zero in order to pace both chamberssimultaneously, positive in order to pace the synchronized chamber afterthe rate chamber, or negative to pace the synchronized chamber beforethe rate chamber. One example of such pacing is biventricular offsetsynchronized pacing where both ventricles are paced with a specifiedoffset interval. The rate ventricle is paced in accordance with asynchronous bradycardia mode which may include atrial tracking, and theventricular escape interval is reset with either a pace or a sense inthe rate ventricle. (Resetting in this context refers to restarting theinterval in the case of an LRL ventricular escape interval and tostopping the interval in the case of an AVI.) Thus, a pair ofventricular paces are delivered after expiration of the AVI escapeinterval or expiration of the LRL escape interval, with ventricularpacing inhibited by a sense in the rate ventricle that restarts the LRLescape interval and stops the AVI escape interval. In this mode, thepumping efficiency of the heart will be increased in some patients bysimultaneous pacing of the ventricles with an offset of zero. However,it may be desirable in certain patients to pace one ventricle before theother in order to compensate for different conduction velocities in thetwo ventricles, and this may be accomplished by specifying a particularpositive or negative ventricular offset interval.

Another synchronized mode is triggered synchronized pacing. In one typeof triggered synchronized pacing, the synchronized chamber is pacedafter a specified trigger interval following a sense in the ratechamber, while in another type the rate chamber is paced after aspecified trigger interval following a sense in the synchronizedchamber. The two types may also be employed simultaneously. For example,with a trigger interval of zero, pacing of one chamber is triggered tooccur in the shortest time possible after a sense in the other chamberin order to produce a coordinated contraction. (The shortest possibletime for the triggered pace is limited by a sense-to-pace latency perioddictated by the hardware.) This mode of pacing may be desirable when theintra-chamber conduction time is long enough that the pacemaker is ableto reliably insert a pace before depolarization from one chamber reachesthe other. Triggered synchronized pacing can also be combined withoffset synchronized pacing such that both chambers are paced with thespecified offset interval if no intrinsic activity is sensed in the ratechamber and a pace to the rate chamber is not otherwise delivered as aresult of a triggering event. A specific example of this mode isventricular triggered synchronized pacing where the rate andsynchronized chambers are the right and left ventricles, respectively,and a sense in the right ventricle triggers a pace to the left ventricleand/or a sense in the left ventricle triggers a pace to the rightventricle.

As with other synchronized pacing modes, the rate chamber in a triggeredsynchronized pacing mode can be paced with one or more synchronousbradycardia pacing modes. If the rate chamber is controlled by atriggered bradycardia mode, a sense in the rate chamber sensing channel,in addition to triggering a pace to the synchronized chamber, alsotriggers an immediate rate chamber pace and resets any rate chamberescape interval. The advantage of this modal combination is that thesensed event in the rate chamber sensing channel might actually be afar-field sense from the synchronized chamber, in which case the ratechamber pace should not be inhibited. In a specific example, the rightand left ventricles are the rate and synchronized chambers,respectively, and a sense in the right ventricle triggers a pace to theleft ventricle. If right ventricular triggered pacing is also employedas a bradycardia mode, both ventricles are paced after a rightventricular sense has been received to allow for the possibility thatthe right ventricular sense was actually a far-field sense of leftventricular depolarization in the right ventricular channel. If theright ventricular sense were actually from the right ventricle, theright ventricular pace would occur during the right ventricle'sphysiological refractory period and cause no harm.

As mentioned above, certain patients may experience some cardiacresynchronization from the pacing of only one ventricle and/or oneatrium with a conventional bradycardia pacing mode. It may be desirable,however, to pace a single atrium or ventricle in accordance with apacing mode based upon senses from the contralateral chamber. This mode,termed synchronized chamber-only pacing, involves pacing only thesynchronized chamber based upon senses from the rate chamber. One way toimplement synchronized chamber-only pacing is to pseudo-pace the ratechamber whenever the synchronized chamber is paced before the ratechamber is paced, such that the pseudo-pace inhibits a rate chamber paceand resets any rate chamber escape intervals. Such pseudo-pacing can becombined with the offset synchronized pacing mode using a negativeoffset to pace the synchronized chamber before the rate chamber and thuspseudo-pace the rate chamber, which inhibits the real scheduled ratechamber pace and resets the rate chamber pacing escape intervals. Oneadvantage of this combination is that sensed events in the rate chamberwill inhibit the synchronized chamber-only pacing, which may benefitsome patients by preventing pacing that competes with intrinsicactivation (i.e., fusion beats). Another advantage of this combinationis that rate chamber pacing can provide backup pacing when in asynchronized chamber-only pacing mode, such that when the synchronizedchamber pace is prevented, for example to avoid pacing during thechamber vulnerable period following a prior contraction, the ratechamber will not be pseudo-paced and thus will be paced upon expirationof the rate chamber escape interval. Synchronized chamber-only pacingcan be combined also with a triggered synchronized pacing mode, inparticular with the type in which the synchronized chamber is triggeredby a sense in the rate chamber. One advantage of this combination isthat sensed events in the rate chamber will trigger the synchronizedchamber-only pacing, which may benefit some patients by synchronizingthe paced chamber contractions with premature contralateral intrinsiccontractions.

An example of synchronized chamber-only pacing is left ventricle-onlysynchronized pacing where the rate and synchronized chambers are theright and left ventricles, respectively. Left ventricle-onlysynchronized pacing may be advantageous where the conduction velocitieswithin the ventricles are such that pacing only the left ventricleresults in a more coordinated contraction by the ventricles than withconventional right ventricular pacing or biventricular pacing. Leftventricle-only synchronized pacing may be implemented in inhibiteddemand modes with or without atrial tracking, similar to biventricularpacing. A left ventricular pace is then delivered upon expiration of theAVI escape interval or expiration of the LRL escape interval, with leftventricular pacing inhibited by a right ventricular sense that restartsthe LRL escape interval and stops the AVI escape interval.

In the synchronized modes described above, the rate chamber issynchronously paced with a mode based upon detected intrinsic activityin the rate chamber, thus protecting the rate chamber against pacesbeing delivered during the vulnerable period. In order to providesimilar protection to a synchronized chamber or synchronized pacingsite, a synchronized chamber protection period (SCPP) may be provided.(In the case of multi-site synchronized pacing, a similar synchronizedsite protection period may be provided for each synchronized site.) TheSCPP is a programmed interval which is initiated by sense or paceoccurring in the synchronized chamber during which paces to thesynchronized chamber are inhibited. For example, if the right ventricleis the rate chamber and the left ventricle is the synchronized chamber,a left ventricular protection period LVPP is triggered by a leftventricular sense which inhibits a left ventricular pace which wouldotherwise occur before the escape interval expires. The SCPP may beadjusted dynamically as a function of heart rate and may be differentdepending upon whether it was initiated by a sense or a pace. The SCPPprovides a means to inhibit pacing of the synchronized chamber when apace might be delivered during the vulnerable period or when it mightcompromise pumping efficiency by pacing the chamber too close to anintrinsic beat. In the case of a triggered mode where a synchronizedchamber sense triggers a pace to the synchronized chamber, the pacingmode may be programmed to ignore the SCPP during the triggered pace.Alternatively, the mode may be programmed such that the SCPP starts onlyafter a specified delay from the triggering event, which allowstriggered pacing but prevents pacing during the vulnerable period.

In the case of synchronized chamber-only synchronized pacing, asynchronized chamber pace may be inhibited if a synchronized chambersense occurs within a protection period prior to expiration of the ratechamber escape interval. Since the synchronized chamber pace isinhibited by the protection period, the rate chamber is not pseudo-pacedand, if no intrinsic activity is sensed in the rate chamber, it will bepaced upon expiration of the rate chamber escape intervals. The ratechamber pace in this situation may thus be termed a safety pace. Forexample, in left ventricle-only synchronized pacing, a right ventricularsafety pace is delivered if the left ventricular pace is inhibited bythe left ventricular protection period and no right ventricular sensehas occurred.

As noted above, synchronized pacing may be applied to multiple sites inthe same or different chambers. The synchronized pacing modes describedabove may be implemented in a multi-site configuration by designatingone sensing/pacing channel as the rate channel for sensing/pacing a ratesite, and designating the other sensing/pacing channels in either thesame or the contralateral chamber as synchronized channels forsensing/pacing one or more synchronized sites. Pacing and sensing in therate channel then follows rate chamber timing rules, while pacing andsensing in the synchronized channels follows synchronized chamber timingrules as described above. The same or different synchronized pacingmodes may be used in each synchronized channel.

In any of the resynchronization pacing modes discussed above, theeffectiveness of the therapy is increased to the extent that thefrequency of pacing is increased. Accordingly, VRR may be employed toincrease the pacing frequency in a ventricular resynchronization pacingmode by adjusting the filter coefficients in the manner described aboveto result in more paced beats. The LRL adjusted by the VRR filter inthis case then corresponds to the ventricular rate chamber escapeinterval.

FIG. 3B is a system block diagram similar to FIG. 3A but with addedcomponents to illustrate the operation of a ventricularresynchronization pacemaker using VRR. Pacing of the ventricledesignated as the rate ventricle, with or without VRR, is as describedabove with respect to FIG. 3A. In this case, however, expiration of theVEI timer A1 is also detected by synchronized chamber ventricular paceoutput module B2. Module B2 then signals the synchronized ventricularchamber pacing channel B4 to deliver a pacing pulse at a particularpacing instant defined with respect to the expiration of the ventricularescape interval. When VRR is enabled, the ventricular escape interval inthis embodiment is modified in accordance with R-R intervals definedwith respect to the rate chamber. With biventricular sensing, however,either ventricular sensing channel could be used for defining the R-Rintervals. For example, the first detected sense in a cardiac cyclecould be used, or, as an approximation to using the first sense,advantage can be taken of the predominance of left bundle branch blocksin the CHF patient population. In these patients, the right ventricledepolarizes before the left ventricle, and using a right ventricularsense to define the R-R interval is a reasonable approximation for thefirst ventricular sense. This approximation simplifies the VRR andpacing algorithms when right ventricular senses are used to both defineR-R intervals for VRR implementation and to define the cardiac cycle forbradycardia and anti-tachycardia pacing.

5. Implantable Ventricular Cardioverter/Defibrillator with VRR

Tachyarrhythmias are abnormal heart rhythms characterized by a rapidheart rate. Examples of tachyarrhythmias include atrial tachyarrhythmiassuch as atrial tachycardia and atrial fibrillation (AF), and ventriculartachyarrhythmias such as ventricular tachycardia (VT) and ventricularfibrillation (VF). Both ventricular tachycardia and ventricularfibrillation are hemodynamically compromising, and both can belife-threatening. Atrial fibrillation is not immediately lifethreatening, but since atrial contraction is lost, the ventricles arenot filled to capacity before systole which reduces cardiac output. Ifatrial fibrillation remains untreated for long periods of time, it canalso cause blood to clot in the left atrium, possibly forming emboli andplacing patients at risk for stroke.

Cardioversion (an electrical shock delivered to the heart synchronouslywith an intrinsic depolarization) and defibrillation (an electricalshock delivered without such synchronization) can be used to terminatemost tachyarrhythmias, including AF, VT, and VF. As used herein, theterm defibrillation should be taken to mean an electrical shockdelivered either synchronously or not in order to terminate afibrillation. In electrical defibrillation, a current depolarizes acritical mass of myocardial cells so that the remaining myocardial cellsare not sufficient to sustain the fibrillation. The electric shock maythus terminate the tachyarrhythmia by depolarizing excitable myocardium,which thereby prolongs refractoriness, interrupts reentrant circuits,and discharges excitatory foci.

The device in FIG. 2 has a cardioversion/defibrillation functionality asimplemented by a shock pulse generator 50 interfaced to themicroprocessor for delivering shock pulses via a pair of shockelectrodes 51 a and 51 b placed in proximity to regions of the heart.The device may have one such shock pulse generator and shock electrodepair for delivering defibrillation shocks to either the atria or theventricles or may be capable of delivering shocks to both chambers. Thesensing channels are used to both control pacing and for measuring heartrate in order to detect tachyarrhythmias such as fibrillation. Thedevice detects an atrial or ventricular tachyarrhythmia by measuring theatrial or ventricular rate, respectively, as well as possibly performingother processing on data received from the sensing channels.

VRR may be employed in ICDs configured to deliver ventriculardefibrillation shocks and having a pacing capability. Such devices maybe implanted in patients who are prone to ventricular arrhythmias butare not normally in need of either bradycardia or resynchronizationpacing. In these cases, the device may detect a ventriculartachyarrhythmia which does not warrant either a defibrillation shock oranti-tachycardia pacing. VRR pacing may then be initiated in order toimprove the patient's cardiac output and possibly lessen the chance of amore dangerous tachyarrhythmia occurring. The device may be programmedto deliver the VRR therapy for a specified length of time after eachdetection of such a tachyarrhythmia.

FIG. 3C is a block diagram of a ventricular ICD that incorporates theVRR system of FIG. 3A. The ventricular rate is determined by ventricularrate detector C1 which receives input from R-R interval detector A6. Ifventricular fibrillation is detected by the ventricular shock pulseoutput module C2 using a rate-based criterion, a ventriculardefibrillation shock is delivered by ventricular shock pulse generatorC3. If no ventricular fibrillation is present but an irregulartachycardia is detected by the supervisory controller from an input fromrate detector C1, VRR pacing may be initiated for a specified timeperiod.

6. Implantable Atrial Cardioverter/Defibrillator With VRR

VRR may also be employed in devices configured to deliver atrialdefibrillation shocks in order to both maintain hemodynamic stabilityand to more safely deliver the atrial defibrillation shock. In order toavoid the possible induction of ventricular fibrillation, atrialdefibrillation shocks should be delivered synchronously with a sensed Rwave and after a minimum pre-shock R-R interval. This is done becausethe ventricle is especially vulnerable to induction of fibrillation by adepolarizing shock delivered at a time too near the end of the precedingventricular contraction (i.e., close to the T wave on an EKG).Delivering the shock synchronously with a sensed R wave thus moves theshock away from the vulnerable period, but at a very rapid ventricularrhythm, the ventricular beats may be so close together that evensynchronously delivered shocks may induce ventricular fibrillation.Shocking should therefore be delayed until the ventricular rhythm isslow enough to safely deliver the defibrillation pulse as determined bymeasuring the R-R interval. As noted above, however, the intrinsicventricular rhythm during atrial fibrillation tends to be both rapid andirregular. If the intrinsic rhythm could be slowed and made morepredictable, an atrial defibrillation shock could be more safelydelivered.

If AV conduction is intact in a patient, atrial fibrillation results ina very rapid and intrinsic ventricular rhythm, and regularizing theventricular rate improves cardiac output directly through its effect ondiastolic filling. Ventricular rate regularization may be applied inthis instance with parameter settings such that the ventricles aredriven at a rate near the intrinsic rate. The intrinsic ventricularrhythm that occurs during an episode of atrial fibrillation is a resultof the chaotically occurring depolarizations occurring in the atriabeing passed through the AV node to the ventricles. The intrinsicventricular rate is thus governed by the cycle length of the atrialfibrillation and the refractory period of the AV node. If a ventricularpacing pulse is delivered before the next intrinsic beat occurs, theventricular depolarization is conducted retrogradely to the AV nodecausing late depolarization of the AV node during the ventricular beat.The refractory period of the AV node is also delayed, which delays thetime before an atrial depolarization can be conducted through the nodeto result in an intrinsic beat. The effect of the pace is thus tolengthen the time until the next intrinsic beat. Ventricular rateregularization at a pacing rate near the intrinsic ventricular rateduring atrial fibrillation thus not only improves hemodynamics, but alsoincreases the probability that a shockable R-R interval will occur.

FIG. 3D is a block diagram of an atrial ICD that incorporates the VRRsystem of FIG. 3A. P-wave detector D2 determines the amplitude ofsensing signals from atrial sensing channel D1 and outputs a signal toatrial rate detector D3 when a P-wave is detected. The atrial ratedetector determines the atrial rate by measuring the intervals betweenP-waves and, if atrial fibrillation is detected using a rate criterion,VRR pacing may be initiated (or continued) by the supervisory controllerprogram. A signal indicating the presence of atrial fibrillation is alsooutput to atrial shock output module D4 which causes atrial shock pulsegenerator D5 to deliver an atrial defibrillation shock synchronouslywith a detected R-wave if the R-R interval is shockable. The R-Rinterval is measured by the R-R interval detector A6 which sends asignal indicating the measured interval to the module D4. The R-Rinterval is then tested for shockability, and, if a shockable intervalhas occurred, an atrial defibrillation shock is delivered.

Although the invention has been described in conjunction with theforegoing specific embodiment, many alternatives, variations, andmodifications will be apparent to those of ordinary skill in the art.Such alternatives, variations, and modifications are intended to fallwithin the scope of the following appended claims.

1. A cardiac rhythm management device, comprising: a sensing channelconfigurable for sensing depolarizations from a right ventricle;ventricular pacing channels for delivering paces to both right and leftventricles; a controller for controlling the delivery of paces by theventricular pacing channels in accordance with a ventricular escapeinterval that is reset by a right ventricular sense; wherein thecontroller is programmed to pace the left ventricle at a specifiedpacing instant defined with respect to expiration of the ventricularescape interval; and, wherein the controller is further programmed tooperate in a ventricular rate regularization mode in which theventricular escape interval is increased after delivery of a ventricularpace and decreased after a ventricular sense.
 2. The device of claim 1wherein the ventricular escape interval is started by a ventricularsense or pace.
 3. The device of claim 1 further comprising: an atrialsensing channel; and, wherein the ventricular escape interval is startedby an atrial sense.
 4. The device of claim 3 further comprising: anatrial pacing channel; and, wherein the controller is configured todeliver an atrial pace upon expiration of an atrial escape interval andwherein the ventricular escape interval is started by an atrial pace. 5.The device of claim 1 further comprising a sensing channel configurablefor sensing the left ventricle.
 6. The device of claim 1: wherein thecontroller is configured to measure an R-R interval associated with eachventricular sense, an R-R interval being the time between a ventricularsense and a preceding ventricular sense or pace; and, wherein thecontroller is further configured to operate in the ventricular rateregularization mode by adjusting the ventricular escape interval inaccordance with a measured R-R interval.
 7. The device of claim 6further comprising: a filter for increasing the ventricular escapeinterval upon delivery of a ventricular pace; and, a filter fordecreasing the ventricular escape interval upon occurrence of aventricular sense in accordance with the measured R-R interval.
 8. Thedevice of claim 7 wherein the controller is configured to adjust theventricular escape interval by computing a weighted average of themeasured R-R interval multiplied by a scaling factor and the previousvalue of the ventricular escape interval after each ventricular sense,and wherein the ventricular escape interval is adjusted by multiplyingthe escape interval by a decay coefficient after a ventricular pace. 9.The device of claim 1 wherein the controller is configured to beginoperating in the ventricular rate regularization mode upon detection ofan irregular ventricular tachycardia.
 10. The device of claim 1 whereinthe controller is configured to begin operating in the ventricularregularization mode upon detection of atrial fibrillation.
 11. A methodfor operating a cardiac rhythm management device, comprising: sensingdepolarizations from a right ventricle; delivering paces to the leftventricle in accordance with a ventricular escape interval that is resetby a right ventricular sense; pacing the left ventricle at a specifiedpacing instant defined with respect to expiration of the ventricularescape interval; and, operating in a ventricular rate regularizationmode in which the ventricular escape interval is increased afterdelivery of a ventricular pace and decreased after a ventricular sense.12. The method of claim 11 wherein the ventricular escape interval isstarted by a ventricular sense or pace.
 13. The method of claim 11further comprising: sensing atrial depolarizations; and, wherein theventricular escape interval is started by an atrial sense.
 14. Themethod of claim 13 further comprising delivering an atrial pace uponexpiration of an atrial escape interval and wherein the ventricularescape interval is started by an atrial pace.
 15. The method of claim 11further comprising sensing the left ventricle.
 16. The method of claim11: measuring an R-R interval associated with each ventricular sense, anR-R interval being the time between a ventricular sense and a precedingventricular sense or pace; and, operating in the ventricular rateregularization mode by adjusting the ventricular escape interval inaccordance with a measured R-R interval.
 17. The method of claim 16further comprising: increasing the ventricular escape interval upondelivery of a ventricular pace; and, decreasing the ventricular escapeinterval upon occurrence of a ventricular sense in accordance with themeasured R-R interval.
 18. The method of claim 17 further comprisingadjusting the ventricular escape interval by computing a weightedaverage of the measured R-R interval multiplied by a scaling factor andthe previous value of the ventricular escape interval after eachventricular sense, and wherein the ventricular escape interval isadjusted by multiplying the escape interval by a decay coefficient aftera ventricular pace.
 19. The method of claim 11 further comprisingbeginning operation in the ventricular rate regularization mode upondetection of an irregular ventricular tachycardia.
 20. The method ofclaim 11 further comprising beginning operation in the ventricularregularization mode upon detection of atrial fibrillation.